US9708308B2ActiveUtilityA1
Factor IXa inhibitors

Assignee: MERCK SHARP & DOHMEPriority: Dec 19, 2012Filed: Dec 16, 2013Granted: Jul 18, 2017
Est. expiryDec 19, 2032(~6.5 yrs left)· nominal 20-yr term from priority
Inventors:Cameron Smith John Qiang Tan Ting Zhang James M. Balkovec William J. Greenlee Liangqin Guo Yi-Heng Chen Yili Chen Jiayi Xu Samuel Chackalamannil Tomokazu Hirabayashi Hiroshi Nagasue Kouki Ogawa
C07D 471/04C07D 498/04C07D 413/14C07D 417/14A61P 7/02C07D 487/04
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Claims
Abstract

The present invention provides a compound of Formula (I) wherein R 1 is H or C 1-6 alkyl, R 2 , is H or C 1-6 alkyl or CH 2 OH, R 3 is H or C 1-6 alkyl, and R 4 is H or C 1-6 alkyl, provided that when R 1 , R 2 , and R 3 are H, R 4 is C 1-6 alkyl, and when R 1 , R 2 , and R 4 are H, then R 3 is C 1-6 alkyl, and when R 1 , R 3 , and R 4 are H, R 2 is C 1-6 alkyl or —CH 2 OH, and when R 2 , R 3 , and R 4 are H, then R 1 is C 1-6 alkyl; A is 1) a 9-10 membered bicyclic heterocycle having 1-3 heteroatoms independently selected from N, S and O, which 9-10 membered bicyclic heterocycle is unsubstituted or substituted with R 5 and unsubstituted or substituted with R 6 and unsubstituted or substituted with NH 2 , or 2) a 6-9 membered monocyclic or bicyclic carbocyclic ring system unsubstituted or substituted with R 5 , unsubstituted or substituted with R 6 , and unsubstituted or substituted with —CH 2 NH 2 ; and B is 1) a 5- or 6-membered monocyclic heterocycle having 1 or 2 heteroatoms independently selected from N, S or O, which is unsubstituted or substituted on a carbon or nitrogen atom with R 7 , unsubstituted or substituted on a carbon or nitrogen atom with R 8 , and unsubstituted or substituted on a carbon or nitrogen atom with R 9 , or 2) an 8- or 9-membered fused bicyclic heterocycle having 1, 2 or 3 nitrogen atoms which is unsubstituted or substituted on a carbon or nitrogen atom with R 7 , and unsubstituted or substituted on a carbon or nitrogen atom with R 8 ; and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses.
Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A compound of formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R 1  is H or C 1-6  alkyl, R 2 , is H or C 1-6  alkyl or CH 2 OH, R 3  is H or C 1-6  alkyl, and R 4  is H or C 1-6  alkyl,
 provided that when R 1 , R 2 , and R 3  are H, R 4  is C 1-6  alkyl, and when R 1 , R 2 , and R 4  are H, then R 3  is C 1-6  alkyl, and when R 1 , R 3 , and R 4  are H, R 2  is C 1-6  alkyl or —CH 2 OH, and when R 2 , R 3 , and R 4  are H, then R 1  is C 1-6  alkyl; 
 
         A is
 1) a 9-10 membered bicyclic heterocycle having 1-3 heteroatoms independently selected from N, S and O, which 9-10 membered bicyclic heterocycle is unsubstituted or substituted with R 5 , unsubstituted or substituted with R 6 , and unsubstituted or substituted with NH 2 , or 
 2) a 6-9 membered monocyclic or bicyclic carbocyclic ring system unsubstituted or substituted with R 5 , unsubstituted or substituted with R 6 , and unsubstituted or substituted with —CH 2 NH 2 ; 
 
         R 5  is halogen; 
         R 6  is C 1-6 alkyl; 
         B is
 1) a 5- or 6-membered monocyclic heterocycle having 1 or 2 heteroatoms independently selected from N, S or O, which is unsubstituted or substituted on a carbon or nitrogen atom with R 7 , unsubstituted or substituted on a carbon or nitrogen atom with R 8 , and unsubstituted or substituted on a carbon or nitrogen atom with R 9 , or 
 2) an 8- or 9-membered fused bicyclic heterocycle having 1, 2 or 3 nitrogen atoms which is unsubstituted or substituted on a carbon or nitrogen atom with R 7 , and unsubstituted or substituted on a carbon or nitrogen atom with R 8 ; 
 
         R 7  is CF 3 , C 1-6 alkyl, C 1-6 alkanol, C 3-8 carbocycle, aryl, 
       
       
         
           
           
               
               
           
         
         
           or a 5- or 6-membered heterocycle having 1 or 2 nitrogen atoms and zero or 1 oxygen atom, which heterocycle or C 3-8 carbocycle or aryl is unsubstituted or mono-, di-, tri- or tetra-substituted with a group independently selected from R 10 , R 11 , R 12 , R 13 , and R 15 ; 
         
         R 8  is C 1-6 alkyl; 
         R 9  is halogen; 
         R 10  is CF 3 , CN, C(O)NH 2 , OCD 3 , OC 1-6 alkyl, OCH(CH 2 Cl)(CH 2 OH),
 —OC 3-8 cycloalkyl, or 
 
       
       
         
           
           
               
               
           
         
         R 11  is halogen, C 1-6 alkyl, CF 3 , CHF 2 , CN, or COOH; 
         R 12  is CF 3 , COOH, C(O)OC 1-6 alkyl, CN, halogen, OCF 3 , ═O, or SO 2 C 1-6 alkyl; 
         R 13  is C 1-6 alkyl, C(O)OC 1-6 alkyl, CN, CF 3 , OC 1-6 alkyl, N(C 1-6 alkyl) 2 , OC 1-6 alkyl, or OCHF 2 ; and 
         R 15  is halogen, CF 3 , CHF 2 , C 1-6 alkyl, CN, or COOH. 
       
     
     
       2. A compound of formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R 1  is H or C 1-6  alkyl, R 2 , is H or C 1-6  alkyl or CH 2 OH, R 3  is H or C 1-6  alkyl, and R 4  is H or C 1-6  alkyl,
 provided that when R 1 , R 2 , and R 3  are H, R 4  is C 1-6  alkyl, and when R 1 , R 2 , and R 4  are H, then R 3  is C 1-6  alkyl, and when R 1 , R 3 , and R 4  are H, R 2  is C 1-6  alkyl or —CH 2 OH, and when R 2 , R 3 , and R 4  are H, then R 1  is C 1-6  alkyl; 
 
         A is 
       
       
         
           
           
               
               
           
         
         R 5  is halogen; 
         R 6  is C 1-6 alkyl; 
         B is 
       
       
         
           
           
               
               
           
         
         R 7  is CF 3 , C 1-6 alkyl, C 1-6 alkanol, or C 3-8 carbocycle, 
       
       
         
           
           
               
               
           
         
         R 8  is C 1-6 alkyl; 
         R 9  is halogen; 
         R 10  is CF 3 , CN, C(O)NH 2 , OD 3 , OC 1-6 alkyl, OCH(CH 2 Cl)(CH 2 OH), —OC 3-8 cycloalkyl, or 
       
       
         
           
           
               
               
           
         
         R 11  is halogen, C 1-6 alkyl, CF 3 , CHF 2 , CN, or COOH; 
         R 12  is CF 3 , COOH, C(O)OC 1-6 alkyl, CN, halogen, OCF 3 , ═O, or SO 2 C 1-6 alkyl; 
         R 13  is C 1-6 alkyl, C(O)OC 1-6 alkyl, CN, CF 3 , OC 1-6 alkyl, N(C 1-6 alkyl) 2 , OC 1-6 alkyl, or OCHF 2 ; and 
         R 15  is halogen, CF 3 , CHF 2 , C 1-6 alkyl, CN, or COOH. 
       
     
     
       3. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein A is 
       
         
           
           
               
               
           
         
       
     
     
       4. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein B is 
       
         
           
           
               
               
           
         
       
     
     
       5. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 7  is CF 3 , CH 3 , C(CH 3 ) 2 OH, cyclopropyl, 
       
         
           
           
               
               
           
         
       
     
     
       6. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 R 5  is Cl, or F; 
 R 6  is CH 3 ; 
 R 8  is CH 3 ; 
 R 9  is F; 
 R 10  is CF 3 , CN, C(O)NH 2 , OCH 2 CH 3 , OD 3 , OCH 3 , OC(CH 3 ) 3 , OCH(CH 3 ) 2 , OCH(CH 2 Cl)(CH 2 OH), 
 
       
         
           
           
               
               
           
         
         R 11  is F, Cl, Br, CH 3 , CF 3 , CHF 2 , CN, COOH; 
         R 12  is CF 3 , COOH, C(O)OCH 3 , CN, F, Cl, OCF 3 , SO 2 CH 3 ; 
         R 13  is CH 3 , C(O)OCH 3 , CN, CF 3 , OCH 3 , N(CH 3 ) 2 , OCH 2 CH 3 , OCH(CH 3 ) 2 , OCHF 2 ; 
         R 15  is F, Cl, Br, CF 3 , CHF 2 , CH 3 , CN, COOH. 
       
     
     
       7. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 R 1  is H or CH 3 , R 2  is H, CH 3 , CH 2 CH 3 , or CH 2 OH, R 3  is H or CH 3 , and R 4  is H or CH 3 , provided that at least one of the group of R 1 , R 2 , R 3 , and R 4  is CH 3  or, when R 1 , R 3  and R 4  are H, then R 2  is CH 3 , CH 2 CH 3 , or CH 2 OH; 
 A is 
 
       
         
           
           
               
               
           
         
         R 5  is Cl, or F; 
         R 6  is CH 3 ; 
         B is 
       
       
         
           
           
               
               
           
         
         R 7  is CF 3 , CH 3 , C(CH 3 ) 2 OH, cyclopropyl, 
       
       
         
           
           
               
               
           
         
         R 8  is CH 3 ; 
         R 9  is F; 
         R 10  is CF 3 , CN, C(O)NH 2 , OCH 2 CH 3 , OCD 3 , OCH 3 , OC(CH 3 ) 3 , OCH(CH 3 ) 2 , OCH(CH 2 Cl)(CH 2 OH) 
       
       
         
           
           
               
               
           
         
         R 11  is F, Cl, Br, CH 3 , CF 3 , CHF 2 , CN, COOH; 
         R 12  is CF 3 , COOH, C(O)OCH 3 , CN, F, Cl, OCF 3 , SO 2 CH 3 ; 
         R 13  is CH 3 , C(O)OCH 3 , CN, CF 3 , OCH 3 , N(CH 3 ) 2 , OCH 2 CH 3 , OCH(CH 3 ) 2 , OCHF 2 ; and 
         R 15  is F, Cl, Br, CF 3 , CHF 2 , CH 3 , CN, COOH. 
       
     
     
       8. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1  and R 2  are H, and R 3  and R 4  are CH 3 . 
     
     
       9. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2  and R 3  are H, and R 4  is CH 3 . 
     
     
       10. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3  and R 4  are H, and R 1  is CH 3 . 
     
     
       11. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 3  and R 4  are H, and R 2  is CH 3 . 
     
     
       12. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1  and R 2  are CH 3 , and R 3  and R 4  are H. 
     
     
       13. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 3  and R 4  are H, and R 2  is CH 2 OH. 
     
     
       14. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 3  and R 4  are H, and R 2  is CH 2 CH 3 . 
     
     
       15. A compound of  claim 2 , or a pharmaceutically acceptable salt thereof, which is
 (2R)—N-(3-Amino-1,2-benzoxazol-6-yl)-2-hydroxy-2-[(2R)-4-[1-(2-methoxy-4-pyridyl)pyrazol-3-yl]-3-oxo-morpholin-2-yl]propanamide, 
 (R)—N-(3-Aminoisoxazolo[4,5-b]pyridin-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-(R)-4-(1-(6-cyanopyridazin-4-yl)-5-methyl-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-(R)-4-(1-(6-ethoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 5-(3-((R)-2-((R)-1-((3-Aminobenzo[d]isoxazol-6-yl)amino)-2-hydroxy-1-oxopropan-2-yl)-3-oxomorpholino)-1H-pyrazol-1-yl)pyridazine-3-carboxamide, 
 (2R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((2R)-4-(1-(6-((1-chloro-3-hydroxypropan-2-yl)oxy)pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-methyl-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(4-fluorophenyl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 4-(3-((R)-2-((R)-1-((3-aminobenzo[d]isoxazol-6-yl)amino)-2-hydroxy-1-oxopropan-2-yl)-3-oxomorpholino)-1H-pyrazol-1-yl)benzoic acid, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(3-chloro-4-cyanophenyl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(4-fluorophenyl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methylpyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-ethoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-isopropoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-(dimethylamino)pyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(5-bromo-2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(5-fluoro-2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(5-chloro-2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxy-5-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-cyanopyridin-4-yl)-4-fluoro-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-chloro-1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-chloro-1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-4-methyl-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-5-methyl-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-(azetidin-1-yl)pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (2R)—N-(3-amino-1,2-benzoxazol-6-yl)-2-hydroxy-2-[(2R)-3-oxo-4-[1-[6-(trideuteriomethoxy)pyridazin-4-yl]pyrazol-3-yl]morpholin-2-yl]propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-isopropoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-(tert-butoxy)pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyclobutoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(1-methyl-6-oxo-1,6-dihydropyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyanopyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyanopyridazin-4-yl)-4-fluoro-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methylpyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-(dimethylamino)pyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(2-(trifluoromethyl)pyrimidin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-cyanopyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-methoxypyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(2-(trifluoromethyl)pyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(2-methoxypyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(5-methyl-1-(2-(trifluoromethyl)pyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(5-(pyridin-4-yl)furan-2-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(5-(2-cyanopyridin-4-yl)furan-2-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(5-(2-(trifluoromethyl)pyridin-4-yl)furan-2-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(5-(2-methoxypyridin-4-yl)furan-2-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(5-(2-methoxypyrimidin-4-yl)furan-2-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(6-(trifluoromethyl)pyridin-2-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(6-(pyridazin-4-yl)pyridin-2-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(6-(trifluoromethyl)quinolin-2-yl)morpholin-2-yl)propanamide, 
 (R)-2-((R)-4-(1,7-naphthyridin-2-yl)-3-oxomorpholin-2-yl)-N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(5,6-dihydro-4H-pyrrlo[1,2-b]pyrazol-2-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(6-(trifluoromethyl)pyridin-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-2-ethyl-3-oxo-4-(6-(trifluoromethyl)pyridin-2-yl)morpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-(hydroxymethyl)-3-oxo-4-(6-(trifluoromethyl)pyridin-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(4-fluorophenyl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(4-cyanophenyl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 methyl 4-(3-((R)-2-((R)-2-((3-aminobenzo[d]isoxazol-6-yl)amino)-1-hydroxy-2-oxoethyl)-2-methyl-3-oxomorpholino)-1H-pyrazol-1-yl)benzoate, 
 4-(3-((R)-2-((R)-2-((3-aminobenzo[d]isoxazol-6-yl)amino)-1-hydroxy-2-oxoethyl)-2-methyl-3-oxomorpholino)-1H-pyrazol-1-yl)benzoic acid, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(4-chlorophenyl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-4-(1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridin-3-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(5-(trifluoromethyl)pyridin-3-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(5-cyanopyridin-3-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(3-fluoropyridin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 methyl 4-(3-((R)-2-((R)-2-((3-aminobenzo[d]isoxazol-6-yl)amino)-1-hydroxy-2-oxoethyl)-2-methyl-3-oxomorpholino)-1H-pyrazol-1-yl)picolinate, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(3,5-difluoropyridin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-4-(5-methyl-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridazin-4-yl)-1 H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)acetamide, 
 (2R)—N-(3-amino-1,2-benzoxazol-6-yl)-2-hydroxy-2-[(2R)-2-methyl-3-oxo-4-[1-[6-(trideuteriomethoxy)pyridazin-4-yl]pyrazol-3-yl]morpholin-2-yl]acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyanopyridazin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyrimidin-5-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(2-(trifluoromethyl)pyrimidin-5-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyrimidin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-cyclopropyl-5-methyl-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(4-(pyridin-4-yl)oxazol-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(4-(pyridin-4-yl)thiazol-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(2-(pyridin-4-yl)thiazol-4-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(6-((tetrahydro-2H-pyran-4-yl)oxy)pyridin-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(6-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)morpholin-2-yl)acetamide, 
 4-(6-((R)-2-((R)-2-((3-aminobenzo[d]isoxazol-6-yl)amino)-1-hydroxy-2-oxoethyl)-2-methyl-3-oxomorpholino)pyridin-2-yl)benzoic acid, 
 2-(6-((R)-2-((R)-2-((3-aminobenzo[d]isoxazol-6-yl)amino)-1-hydroxy-2-oxoethyl)-2-methyl-3-oxomorpholino)pyridin-2-yl)-5-(trifluoromethyl)benzoic acid, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(6-(pyridazin-4-yl)pyridin-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(6-(2-(trifluoromethyl)pyrimidin-5-yl)pyridin-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(6-(isoxazol-4-yl)pyridin-2-yl)-2-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-4-(6-(3-methylisoxazol-4-yl)pyridin-2-yl)-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(6-(3,5-dimethylisoxazol-4-yl)pyridin-2-yl)-2-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-4-(1,7-naphthyridin-2-yl)-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(6-(trifluoromethyl)-1,7-naphthyridin-2-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyanopyridazin-4-yl)-4-fluoro-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-4-(1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-amino-4-chlorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methylpyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(pyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-(azetidin-1-yl)pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-isopropoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyanopyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(pyridazin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)-2-hydroxypropanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyrimidin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-amino-4-fluorobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyrimidin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminoisoxazolo[4, 5-b]pyridin-6-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-chloro-2-methyl-1H-indol-5-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(3-chloro-2-methyl-1H-indol-5-yl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(4-aminoquinazolin-7-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-2-methyl-3-oxomorpholin-2-yl)propanamide, 
 (R)—N-(4-(aminomethyl)phenyl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(4-(aminomethyl)-3-fluorophenyl)-2-hydroxy-2-((R)-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)propanamide, 
 (R)—N-(4-(aminomethyl)phenyl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(4-(aminomethyl)-3-fluorophenyl)-2-hydroxy-2-((R)-2-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((2R,6R)-4-(1-(6-cyanopyridazin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((2R,6S)-4-(1-(6-cyanopyridazin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-Aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(1-(6-cyanopyridazin-4-yl)-1H-pyrazol-3-yl)-6,6-dimethyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6R)-6-methyl-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((2R,6R)-4-(4-fluoro-1-(pyridazin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6R)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6 S)-6-methyl-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((2R,6 S)-4-(4-fluoro-1-(pyridazin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6 S)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6 S)-6-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((2R,6S)-4-(1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((2R,6R)-4-(1-(2-cyanopyridin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6R)-6-methyl-3-oxo-4-(1-(pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6 S)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6R)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-6-methyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6S)-6-methyl-3-oxo-4-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((2R,6R)-6-methyl-3-oxo-4-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(2-methoxypyridin-4-yl)-1H-pyrazol-3-yl)-6,6-dimethyl-3-oxomorpholin-2-yl)acetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-6,6-dimethyl-3-oxo-4-(1-(pyridazin-4-yl)-1H-pyrazol-3-yl)morpholin-2-yl)-2-hydroxyacetamide, 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-((R)-4-(4-fluoro-1-(pyridazin-4-yl)-1H-pyrazol-3-yl)-6,6-dimethyl-3-oxomorpholin-2-yl)-2-hydroxyacetamide, or 
 (R)—N-(3-aminobenzo[d]isoxazol-6-yl)-2-hydroxy-2-((R)-4-(1-(6-methoxypyridazin-4-yl)-1H-pyrazol-3-yl)-6,6-dimethyl-3-oxomorpholin-2-yl)acetamide. 
 
     
     
       16. A composition for inhibiting thrombus formation in blood comprising a compound of  claim 2  and a pharmaceutically acceptable carrier.
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